The invention relates to an improved enteral nutritional formula and more particularly to infant formulas which contain a lipid fraction possessing a fatty acid profile resulting in more desirable infant stool patterns compared to stool patterns associated with conventional infant formula. More specifically, this invention relates to a blend of high oleic safflower oil, and/or high oleic sunflower oil, soy oil and coconut oil (or a blend of fats that have a similar fatty acid profile to the inventive blend) that has been found effective in producing stool patterns in infants that are similar to those of the breast-fed infant.
The composition of human milk serves as a valuable reference for improving infant formula. However, human milk contains living cells, hormones, active enzymes, immunoglobulins and components with unique molecular structures that cannot be replicated in infant formula. Unlike human milk, infant formula must remain stable on the shelf for up to thirty-six (36) months. These fundamental differences between human milk and infant formula often mandate differences in the composition to achieve similar clinical outcome.
The study of human milk components has stimulated many investigations into what constituents may be added to an improved infant formula. Greater knowledge of the composition of human milk affords the opportunity to design infant formulas that are closer in composition to human milk. However, it becomes increasingly apparent that infant formula can never exactly duplicate human milk. Many constituents in human milk are bioactive and because of synergies among these components, there is little reason to believe that the same compound would have the same bioactivity in infant formula. The likelihood of this possibility is further diminished when the impact of heat treatment for sterilization and long-term storage of the formula is considered. The present invention is based, in part, on the concept of providing a formula which matches the performance of breast milk in stool consistency parameters without attempting to duplicate exactly the delicate balance of human milk components.
The composition of human milk differs appreciably from that of other species and much attention has been paid to the various components. Several investigators have reported on the nucleotide content of milk from humans (Janas, L M et al: The Nucleotide Profile of Human Milk. Pediatr. Res. 16:659-662(1982) and Gil et al.: Acid-soluble Nucleotides of Human Milk at Different Stages of Lactation. Journal of Dairy Research (1982), 49, 301-307). Numerous publications have also discussed various lipid, oil or fat blends for use in an artificial nutritional for human infants. As the result of investigations regarding the use of nucleotides in infant formula, the inventors of the present application discovered that a particular blend of oils resulted in infant stool patterns that are similar to those of the breast fed infant.
Formula tolerance is generally assessed by gastrointestinal symptoms (e.g., emesis, stool patterns and gas) as well as behavioral characteristics (e.g., acceptance of formula, fussing and crying). Concerns regarding poor tolerance are frequently reported as a reason for formula switching within the first two months of life. (Forsythe B W C, McCarthy P L, Leventhal J M: Problems of early infancy, formula changes, and mother""s beliefs about their infants. J. Pediatr. 1985; 106:1012-1017). Stool patterns are known to differ between formula-fed and breast-fed infants, (Weaver L T, Ewing G. Taylor, L C: The Bowel Habit of Milk-Fed Infants. J. Pediatr. Gastroenterol Nutr. 1988; 7:568-571), as well as between infants fed various formulas (Hyarns, J S, Treem W R, Etienne N L, et al.: Effect of infant formula on stool characteristics of young infants. Pediatrics 19951 50:54).
The Hyams et al. publication, supra, also reports that certain infant formulas typically cause a significantly greater percentage of firm stools compared to the breast-fed infant which may be perceived by the parent or care giver as unacceptable. This publication also indicated that milk-based, iron-fortified formulas resulted in a significantly lower percentage of watery stools. S. J. Fomon in Nutrition of Normal Infants (L. Craven ed.) Mosby: St. Louis, Mo., at page 250 states that xe2x80x9cMany physicians appear to be convinced that infants fed iron-fortified formulas are prone to fussiness . . . and constipation.xe2x80x9d It is this problem and/or perception that the present invention addresses. Quinlan et al. in Pediatr Gastroenteral Nutr., Vol. 20, No. 1 (1995) concludes that xe2x80x9cConstipationxe2x80x9d and xe2x80x9chard stoolsxe2x80x9d are associated with formula feeding of both term and pre-term infants and, in the latter, can lead to life threatening complications.xe2x80x9d
Numerous investigators have reported that fatty acid profiles similar to human milk are important to the human infant. Representative of those numerous publications are: 1) Gil et al., changes in the Fatty acid Profiles of Plasma Lipid Fractions Induced by Dietary Nucleotides in Infants Born at Term, Eur. J. of C. Nutrition, (1988) 42, 473-481; 2) E.P. 0129,990; 3) E.P. 0376,628; 4) U.S. Pat. No. 4,670,285; 5) U.S. Pat. No. 3,231,385; 6) U.S. Pat. No. 4,544,559; 7) U.S. Pat. No. 4,758,553; and 8) U.S. Pat. No. 4,994,442. These investigators have failed to discover that a blend of lipid sources, which is essentially free of palmitic acid which may comprise a blend of high oleic safflower oil, soy oil and coconut oil, is beneficial in overcoming certain shortcomings associated with infant formula.
Previous investigations have attempted to duplicate the fatty acid profile of human milk in an effort to improve infant formula. In contrast, the present invention is based upon discovery that a particular fatty acid profile for the lipid not closely related to the profile of human milk, will result in a stool pattern similar to breast fed infants while also supplying basic nutritional requirements. Such a lipid profile can be achieved, for example, through a blend of oils.
The enteral formula of the instant invention provides a positive advantage to the infant. The clinical studies which were conducted and reported herein evidence the unexpected advantages of the instant invention. An additional aspect of the present invention is the overall balance of nutrient interactions and bio-availability, which provide an improved nutritional product. Another aspect of the present invention relates to an infant formula which meets the requirements of the Infant Formula Act and to methods for reducing the incidence of objectionable stool characteristics associated with conventional infant formula. Further, the present invention is directed to a novel blend of oils which provide a fatty acid profile that is beneficial in human nutrition.
Thus, the invention provides, in one aspect an improved fat composition for consumption by humans characterized by a fatty acid profile comprising 9.5-21 weight % lauric acid, up to 10 weight % palmitic acid and 34-48 weight % oleic acid. In another aspect, the invention provides an enteral formula comprising protein, carbohydrate and a fat composition as described above.
Yet another aspect of the invention provides a method of improving the stool pattern of a formula-fed infant and a method for reducing the incidence of constipation associated with ingestion of infant formula comprising feeding the infant a formula comprising a fat blend as described above. More specifically, the inventive method comprises feeding an infant a nutritionally complete formula comprising a weight ratio of lauric acid to palmitic acid to oleic acid that ranges from 4:3:8 to 1:0.5:3 with a preferred ratio at 2:1:6.
Even more specifically, this invention relates to an infant formula which comprises a source of amino nitrogen, carbohydrates and fat, the improvement characterized in a fat composition comprising 10.4-15.4 weight % lauric acid, 7.5-8.0 weight % palmitic acid and 37.6-43.0 weight % oleic acid and wherein the fat composition is derived from a mixture of oils selected from the group consisting of high oleic safflower oil, high oleic sunflower, soy, coconut, safflower and palm kernel oil.
Further, this invention discloses a method of improving the stool pattern of a formula-fed infant comprising feeding the infant a nutritionally complete composition containing fatty acids, which, based upon the total weight of fatty acid content comprises 10.4-15.0% lauric acid, 7.5-8.0% palmitic acid and 37.6-43.0% oleic acid and wherein the fatty acids are derived from a mixture of high oleic safflower oil, soy oil and coconut oil.
The term xe2x80x9cfatty acid profilexe2x80x9d as used herein means the total fatty acid content of the fat, oil, emulsifiers and other components used to create an enteral nutritional as determined by convention analysis. Unless specified otherwise, all percentages are weight percents of total fatty acid content. Those skilled in the art will appreciate that sometimes the levels of fatty acids are reported as grams of fatty acid per 100 grams of fat.
In one embodiment, the invention relates to an enteral formula, said formula comprising: 1) protein, said protein being of a concentration of between 10 and 35 grams per liter of formula; 2) carbohydrates, said carbohydrates being of a concentration of between 70 and 110 grams per liter of formula; and 3) fat, said fat having a fatty acid profile comprising 9.5-21 weight percent lauric acid, up to 10 weight % palmitic acid and 34-48 weight % oleic acid. The enteral formula according to this invention provides a source of carbohydrates selected from sucrose, corn syrup, glucose polymers and other carbohydrate sources. The formula may also contain dietary fiber. The teachings of U.S. Pat. No. 5,021,245 are incorporated herein by reference.
(a) In another embodiment, the fat blend further comprises 2.7-3.1 weight % stearic acid, 17-29 weight % linoleic acid and 1.7-3.2 weight % linolenic acid. The fat blend having the recited fatty acid profile can be achieved through a blend of high oleic safflower oil, soy oil and coconut oil. In general, any appropriate source of fatty acids, such as oils, fats, phospholipids, emulsifiers, tissue extracts, single cell oils, recombinant plants, transgenic plants and animals and animals and the like, can be used in this invention, provided less than 10% by weight of total fatty acids is palmitic acid. In an additional embodiment of this invention the weight ratio of linoleic acid to palmitic acid always exceeds 2:1. A further aspect of the invention resides in the discovery of a fatty acid profile for an enteral formula that possesses up to 10 weight % palmitic acid and a weight ratio of lauric acid to palmitic acid to oleic acid of from 3:1:7 to 1.2:1:4.3. The most preferred ratio is about 1.8:1:5.2.
An enteral formula in accordance with the invention may also comprise a nutritionally adequate source of amino nitrogen, carbohydrates, fats, minerals and vitamins, wherein the fat composition consists essentially of 35-55% by weight high oleic safflower oil; 20-40% by weight soy oil; and 20-45% by weight of coconut oil.
The enteral formulas of the invention may be in the form of a ready-to-feed product, a powder or a concentrate. Dilution or reconstitution instructions supplied by the manufacturer should be followed. Those skilled in the art can determine from the instruction conversion factors that would convert the values of such as 10-35 grams per liter of formula for the ready-to-feed product to values applicable to the powdered and concentrate forms.
As used herein, the term xe2x80x9chigh oleic safflower oilxe2x80x9d (HOSO) means the oil derived from the seeds of a hybrid safflower plant, Carthamus tinctorius. Safflower oil is an edible oil which typically has a high content of linoleic acid. Hybrids of this plant have been developed which produce a seed oil which has an elevated level of oleic acid. It is the oil that is derived from the seeds of these hybrids which have been found useful in the present invention. Virtually interchangeable with HOSO is high oleic sunflower oil. Like HOSO, high oleic sunflower oil contains an elevated level of oleic acid. When used herein, the term xe2x80x9cHOSOxe2x80x9d includes its sunflower relative.
As used herein, the term xe2x80x9csoy oilxe2x80x9d (SO) means the fat fraction obtained from the seeds of the legume, Soja max. Typically, the oil fraction of the soya seed undergoes a number of refining, bleaching and deodorization steps resulting in the commercial commodity. Soy oil generally contains relatively high levels of linoleic fatty acid and to a lesser extent, linolenic fatty acid.
As used herein, the term xe2x80x9ccoconut oilxe2x80x9d (CO) means the oil obtained from copra, which is dried coconut meat. This oil is distinguished from HOSO and SO by its high content of saturated, short-chain and medium chain fatty acids. Palm kernel oil is very similar in fatty acid profile to CO. When used herein, the term xe2x80x9cCOxe2x80x9d includes its palm kernel relative.
As used herein, the terms xe2x80x9cstool patternxe2x80x9d and xe2x80x9cconstipationxe2x80x9d relate to kinds of defecation that an individual experiences as a result of nutritional intake. To xe2x80x9cimprove the stool pattern of a formula-fed infantxe2x80x9d means to reduce the actual or perceived difference between the feces consistency of breast-fed infants and those fed a conventional infant formula. As reported above, the consumption of typical infant formula results in infant stools that are firmer/harder than the stools resulting from the consumption of human milk. Human milk is considered the xe2x80x9cgold standardxe2x80x9d by parents and professional care givers alike. As set forth in Table IV below, infants fed breast milk have stools that can be described as between watery (rank of 1) and slightly above loose/mushy (rank of 2). In the five point scale used to evaluate stool consistency whereby; watery=1, loose/mushy=2, soft=3, formed=4 and hard=5, a difference of 0.3 to 0.4 accompanied by a shift in stool category (i.e., soft to formed) is considered significant. Constipation in adults is considered as a difficult, incomplete, or infrequent evacuation of the bowels. In infants, the term is similar to adults, but uses the breast-fed infant for comparison. Further, this condition is a matter of an actual or perceived condition by the parent or care giver. The breast-fed infant typically has a higher number of stools per day (from about 2.5 to 3.5 per day) and has stools of a looser or watery consistency compared to formula-fed infants. Thus, for both terms, xe2x80x9cimproving the stool patternxe2x80x9d and xe2x80x9creducing the incidence of constipationxe2x80x9d, means defecation consistency that more closely resembles the breast-fed infant and a stool of a looser consistency.
The formulas of the invention may take the form of a powdered product, a concentrate or a ready-to feed product. Those skilled in the art will readily appreciate what each form of the product will consist of. In similar fashion, the skilled artisan will understand that reconstitution of the powder and concentrate should follow the instructions of the product manufacturer. As contemplated herein, reconstitution should be accomplished with water and not milk, fruit juices or other liquids that contain protein, carbohydrates or fats.
One aspect of this invention resides in the discovery that particular blends of commodity oils result in a fat composition that possesses a special mixture of fatty acids. The fatty acid profile (predominant) of the commodity oils: soy, coconut, safflower, high oleic safflower, high oleic sunflower, palm kernel and palm olein, are set forth in the following Chart I in an effort to further define and characterize these oils.
The fatty acid profile of this invention is compared to Enfamil(copyright) with Iron, (manufactured by the Mead Johnson Division of Bristol-Meyers, New York, N.Y.); Similac(copyright) with Iron (manufactured by the Ross Products Division of Abbott Laboratories, Abbott Park, Ill.) and human milk in the following Chart II:
The following Chart III sets forth the fatty acid profile of various embodiments of the present invention.
The preferred fatty acid profile as set out above can be accomplished through a blend of 38-50 weight % HOSO, 26-40 weight % SO and 22-36 weight % CO. The more preferred fatty acid profile can be accomplished through a blend of 41-44 weight % HOSO, 27-32 weight % SO, and 27-32 weight % CO. The most preferred fatty acid profile can be accomplished through a blend of 42 weight % HOSO, 28 weight % SO and 30 weight % CO.
Clearly, certain embodiments of the inventive lipid blend are distinguished from commercial fat blends and human milk in the content of lauric, linoleic and palmitic fatty acids. The inventive lipid blend is also distinguished from the prior art formula in the weight ratio of oleic to palmitic fatty acids.
One aspect of the present invention resides in the discovery that an infant formula, to attain stool patterns closer to breast-fed infants, should contain a fat component that is less than 10% by weight palmitic acid. An additional aspect of the inventive oil blend is that the weight ratio of linoleic acid to palmitic acid should always exceed 2:1. In an additional refinement, the weight ratio of oleic to palmitic should always exceed 4:1. A further aspect of the invention resides in the discovery that the fatty acid profile of an infant formula should have a weight ratio of lauric acid to palmitic acid to oleic acid of from 3:1:7 to 1.2:1:4.3. A more preferred ratio is about 1.8:1:5.2.
This invention also relates to a method of reducing the incidence of constipation associated with ingestion of infant formula, said method comprising feeding an infant a nutritionally complete formula comprising: 1) protein; 2) fat, said fat being of a concentration of between 20 and 45 grams per liter of formula; and wherein said fat has a fatty acid profile having a weight ratio of lauric acid to palmitic acid to oleic acid of from 4:3:8 to 1:0.5:3. In a more preferred embodiment the weight ratio is 2:1:6.
From another perspective, the present invention reduces the incidence of constipation through the enteral administration of a fat blend wherein the fat comprises a fatty acid profile with less than 10% by weight of palmitic acid. More specifically, there is disclosed is a method of improving the stool pattern of a formula-fed infant, comprising feeding to the infant a formula comprising high oleic safflower oil, soy oil and coconut oil.
An antioxidant system can be used in conjunction with the invention which consists of xcex2-carotene, R,R,R, xcex1-tocopherol and selenium. The level of R,R,R, xcex1-tocopherol can range from 10 to 30 IU per liter of formula. The level of xcex2-carotene can range from 375 to 575 xcexcg per liter of infant formula and the level of selenium can range from 14 to 32 mcg per liter of formula. The selenium used in this aspect of the invention may be delivered in the form of selenate. The teachings of U.S. Pat. No. 5,221,545 are herein incorporated by reference.
In actual use, the formula of this invention may be consumed by any human. More specifically, the novel fat composition of this invention may be incorporated into a formula which is in compliance with accepted levels of vitamins, minerals, micro-components and the like. The amount consumed does not differ from that associated with the normal consumption of commercially available infant formula. The caloric density (i.e., kcals/ml) and caloric distribution (i.e., the relative proportion of calories from fat, protein and carbohydrate) are not critical to this invention but are generally comparable to conventional formulas. As is well know to those skilled in the art, these factors can vary with the intended use of the formula. For example, pre-term, term and toddler infants have somewhat differing caloric density requirements. Also, formulas for specific disease states (e.g., diabetes, pulmonary deficiency and immuno-comprised) will have differing caloric distributions. Those skilled in the art are aware of these differences and will readily adapt the present invention to meet those special needs.
A representative formula for the enteral nutritional product of the invention is set forth in Table I.
The pediatric nutritional formula of this invention is generally prepared using the following method. An appropriate quantity of protein is dispersed in sufficient water or oil to solubilize or suspend it, thereby forming a protein solution/suspension. Typically this protein source would be intact milk proteins and/or hydrolyzed milk proteins. In general, any known source of amino nitrogen can be used in this invention. Representative sources of amino nitrogen include bovine milk proteins, vegetable proteins, free amino acids, recombinant proteins, hydrolyzed proteins and mixtures thereof. A carbohydrate source such as one or more of corn syrup solids, lactose, maltodextrins and sucrose is dissolved in water, thereby forming a carbohydrate solution. A source of dietary fiber, such as soy polysaccharide may also be added. Appropriate minerals are dissolved in water, the carbohydrate solution or oil, so as to form a mineral solution.
Once formed, the three solutions (protein, carbohydrate and mineral) are combined in appropriate quantities with oils and oil soluble vitamins. As used herein, the terms xe2x80x9coilsxe2x80x9d, xe2x80x9cfatsxe2x80x9d, xe2x80x9cphospholipidsxe2x80x9d, xe2x80x9clipidsxe2x80x9d, xe2x80x9clardxe2x80x9d, and xe2x80x9cextractsxe2x80x9d means a source of fatty acids that may be provided in the form of glycerides, phospholipids, free fatty acids, the methyl esters of fatty acids and the like. An additional source of fatty acids is derived from emulsifiers that contain fatty acids. Representative of such emulsifiers are the di-acetyl mono-glyceride esters of tartaric acid. This resulting solution is then heat processed and homogenized. Following processing, water soluble vitamins, iron, choline and other nutrients are added and then nucleotides may be added. The solution is then diluted with water to the appropriate caloric density, approximately 670-725 kcal per liter for term infant formula. The formula is then dispensed into containers and retorted to obtain commercial sterility or packaged aseptically using commercially available techniques and equipment. As prepared, the formula contains appropriate nutrients in compliance with the Infant Formula Act as of the date of this application. It should also be recognized that the formula of this invention can be prepared for use in powdered form or as a concentrated liquid.